The invention provides non-naturally occurring microbial organisms having reduced carbon flux from succinyl-CoA to succinate through an oxidative TCA cycle. The invention also provides methods of reducing carbon flux from succinyl-CoA to succinate through an oxidative TCA cycle using the microbial organisms.
Carbon loss, through excess CO2 production, can come from three main routes in central metabolism: the pentose phosphate pathway, the glyoxylate shunt and the oxidative tricarboxylic acid (TCA) cycle. The main CO2 generating reaction of the pentose phosphate pathway is phosphogluconate dehydrogenase. Enzymes which can contribute to carbon loss in the TCA cycle and glyoxylate shunt include, for example, pyruvate dehydrogenase, pyruvate formate lyase, pyruvate oxidase, alpha-ketoglutarate dehydrogenase, isocitrate dehydrogenase, phosphoenolpyruvate carboxykinase, and malic enzyme.
Carbon loss can also come from other metabolic reactions that include, for example, the glycine cleavage system, formate hydrogen lyase, formate dehydrogenase, glutamate decarboxylase, pyruvate oxidase, acetolactate synthase and 2-oxo-4-methyl-3-carboxypentanoate decarboxylase, aspartate decarboxylase, lysine decarboxylase, diaminopimelate decarboxylase and enzymes involved in fatty acid biosynthesis.
Thus, there exists a need for alternative means for decreasing carbon loss and increasing carbon flux efficiencies. The present invention satisfies this need and provides related advantages as well.